PD-1/PD-L1 抑制剂与化疗治疗肺癌脑转移的疗效比较：系统评价和荟萃分析。

Efficacy of PD-1/PD-L1 Inhibitors versus Chemotherapy in Lung Cancer with Brain Metastases: A Systematic Review and Meta-Analysis.

机构信息

Department of Oncology, Dongguan Institute for Clinical Cancer Research, Affiliated Dongguan People's Hospital, Southern Medical University, 3 Wandao Road South, Dongguan, 523059 Guangdong, China.

Department of Nephrology and Immunology, Dongguan Marina Bay Central Hospital, Dongguan 523900, China.

出版信息

J Immunol Res. 2022 May 20;2022:4518898. doi: 10.1155/2022/4518898. eCollection 2022.

Immune checkpoint inhibitors (ICIs) are widely used to treat local or metastatic lung cancer. However, the efficacy of ICI in patients with brain metastases (BM) from lung cancer is unknown. This study aimed to evaluate the efficacy of PD-1/PD-L1 ICIs compared with chemotherapy for patients with lung cancer with BM. Electronic databases (PubMed, Embase, The Cochrane Library, and Web of Science) were searched. The meta-analysis assessed overall survival (OS) and progression-free survival (PFS) of the PD-1/PD-L1 inhibitors axis and its relationship with pathological type, drug modality, and the treatment line number in patients with BM from lung cancer. We included 694 patients with BM from lung cancer from 11 randomized controlled trials. Statistical analysis showed that compared with chemotherapy, PD-1/PD-L1 inhibitors could significantly prolong OS (hazard ratio (HR) = 0.75, 95%confidence interval (95%CI) = 0.51-0.99) and PFS (HR = 0.65, 95%CI = 0.51-0.80). In the subgroup analysis, ICIs plus chemotherapy improved PFS (HR = 0.60, 95%CI = 0.40-0.80), but not OS (HR = 0.75, 95%CI = 0.30-1.19). The efficacy of ICI monotherapy in patients with BM was significantly different between OS and PFS: OS pooled HR = 0.81 (95%CI = 0.57-1.05) and PFS = 0.78 (95%CI = 0.62-0.94). Among different pathological types, the OS pooled HR was 0.67 (95%CI = 0.39-0.95) for non-small cell lung cancer (NSCLC) and 0.94 (95%CI = 0.56-1.33) for small cell lung cancer (SCLC); the PFS pooled HR was 0.58 (95%CI = 0.39-0.76) for NSCLC and 0.79 (95%CI = 0.65-0.93) for SCLC. Subgroups analysis of treatment line showed that no advantage for OS with ICIs as first-line or subsequent-line therapy, whereas ICIs as first-line (HR = 0.63, 95%CI = 0.53-0.74) and second-line (HR = 0.62, 95%CI = 0.62-0.96) benefitted PFS. This meta-analysis implied that compared with chemotherapy, PD-1/PD-L1 inhibitors significantly improved efficacy treatment of patients with BM from lung cancer. Further studies are needed to confirm the role of ICIs in different pathological types and drug treatment modalities.

免疫检查点抑制剂（ICIs）广泛用于治疗局部或转移性肺癌。然而，ICI 在肺癌脑转移（BM）患者中的疗效尚不清楚。本研究旨在评估 PD-1/PD-L1 ICI 与化疗治疗肺癌伴 BM 患者的疗效。检索了电子数据库（PubMed、Embase、The Cochrane Library 和 Web of Science）。荟萃分析评估了 PD-1/PD-L1 抑制剂轴的总生存期（OS）和无进展生存期（PFS）及其与肺癌 BM 患者的病理类型、药物方式和治疗线数的关系。我们纳入了来自 11 项随机对照试验的 694 例肺癌 BM 患者。统计分析表明，与化疗相比，PD-1/PD-L1 抑制剂可显著延长 OS（风险比（HR）=0.75，95%置信区间（95%CI）=0.51-0.99）和 PFS（HR=0.65，95%CI=0.51-0.80）。在亚组分析中，ICI 联合化疗可改善 PFS（HR=0.60，95%CI=0.40-0.80），但不能改善 OS（HR=0.75，95%CI=0.30-1.19）。ICI 单药治疗 BM 患者的疗效在 OS 和 PFS 之间存在显著差异：OS 汇总 HR=0.81（95%CI=0.57-1.05）和 PFS=0.78（95%CI=0.62-0.94）。在不同的病理类型中，非小细胞肺癌（NSCLC）的 OS 汇总 HR 为 0.67（95%CI=0.39-0.95），小细胞肺癌（SCLC）为 0.94（95%CI=0.56-1.33）；NSCLC 的 PFS 汇总 HR 为 0.58（95%CI=0.39-0.76），SCLC 为 0.79（95%CI=0.65-0.93）。治疗线的亚组分析表明，ICI 作为一线或后续线治疗并未带来 OS 优势，而 ICI 作为一线（HR=0.63，95%CI=0.53-0.74）和二线（HR=0.62，95%CI=0.62-0.96）治疗均有益于 PFS。这项荟萃分析表明，与化疗相比，PD-1/PD-L1 抑制剂显著改善了肺癌 BM 患者的疗效。需要进一步的研究来证实 ICIs 在不同病理类型和药物治疗方式中的作用。